Schistosomiasis is a snail transmitted parasitic disease that impacts human health on a global scale. Vaccines are under development, but none are currently available. Schistosomes have the ability to develop resistance against praziquantel, the antihelminthic of choice. The study of all aspects of the biology of schistosomes is essential for future means of control. This proposal aims to investigate the immunobiological nature of susceptibility of the snail intermediate host Biomphalaria glabrata for Schistosoma mansoni, as this ultimately leads to transmission of schistosomiasis. The M-line strain of B. glabrata has adequate defenses to survive experimental wounding and bacterial infection, yet these snails support the development of S. mansoni I will investigate whether M-line snails uniquely fail to mount a defense response against S. mansoni, whereas other challenges do evoke effective responses. The genes that are expressed by B. glabrata in response to compatible S. mansoni, incompatible Schistosoma haematobium, Gram -and Gram + bacteria, all versus control snails will be catalogued using a combination of three methods that provide complementary information. These are sequencing of expressed sequencing tags (ESTs), of open reading frame ESTs, and of cDNAs resulting from subtractive suppressive hybridization. The resulting expression profiles will show how B. glabrata responds to different challenges, thus providing a context to evaluate the lack of an effective response of B. glabrata to compatible schistosomes. At least 10 ESTs that resemble known defense genes or that are abundantly expressed will be studied to further characterize the internal defenses of B. glabrata. This study will provide insight into the underlying basis of susceptibility for S. mansoni and thus the potential for transmission of schistosomiasis by B. glabrata. As a significant byproduct, 10000 ESTs from B. glabrata will be generated. This research is designed in consultation with other investigators working with Biomphalaria, to maximize its impact for future genome-type projects.